1. Field of the Invention
The present invention relates to a lipid particle useful for transferring nucleic acids such as micro RNA (miRNA), asymmetrical interfering RNA (aiRNA), or small interfering RNA (siRNA) into a cell, a nucleic acid transfer carrier, a compound for manufacturing a nucleic acid transfer carrier, a method for manufacturing a lipid particle, and a gene transfer method.
2. Description of the Related Art
Nucleic acid medicines have a clear mechanism of action for diseases and cause fewer adverse effects, hence they are expected as next-generation pharmaceutical products. For example, nucleic acid medicines utilizing RNA interference (RNAi) can inhibit expression of a target gene by inducing degradation of messenger RNA (mRNA) of a target gene present in a cell. Consequentially, the medicines can relieve or treat symptoms of diseases caused by the abnormal expression of a specific gene or gene family. For the nucleic acid medicines utilizing RNA interference, for example, nucleic acids such as miRNA, aiRNA, or siRNA are used, and in order to cause these nucleic acids to carry out their function, the nucleic acids need to be transferred into a cell.
As a method for effectively transferring the nucleic acid into a cell, a carrier (vector) is generally used, and the carrier (vector) includes viral carriers and non-viral carriers. Many of the viral carriers have not been clarified in terms of pathogenicity, immunogenicity, and safety regarding cytotoxicity. Therefore, it is desirable to use non-viral carriers for clinical application. The nucleic acid is anionic, and accordingly, as the non-viral carriers, cationic carriers that can hold the nucleic acid by electrostatic interaction are used. As the cationic carriers, for example, a cationic liposome using cationic lipids having a specific structure, complexes using a cationic polymer, and the like are generally known. Examples of the cationic liposome include a liposome in which nucleic acids are bonded to the surface of a lipid bilayer membrane by electrostatic interaction, a lipoplex in which nucleic acids are bonded to the surface of a lipid bilayer membrane and interposed between the lipid bilayer membranes, and the like.
For example, Gene Therapy, Vol. 6, page 271, 1999 discloses a liposome consisting of a cationic lipid, 1,2-dioleoyl-3-sn-phosphatidylethanolamine (DOPE), and polyethylene glycol lipid. Moreover, WO2012/000104A1 discloses a lipid particle containing a cationic lipid in an amount of 50 mol % to 85 mol %, and WO2011/0756556A1 discloses a lipid particle using plural cationic lipids. Further, US2013/0017223A1 discloses a lipid particle consisting of a first cationic lipid, a second cationic lipid, a neutral lipid, and a polyethylene glycol lipid. In addition, various complexes using a cationic polymer are known (Journal of Controlled Release 114 (2006), 100-109).
As means for further improving the cationic carrier, for example, an amphoteric liposome obtained by combining cationic lipids with anionic lipids is disclosed in JP2011-21026A, and an amphoteric liposome consisting of an amphoteric-amphiphilic lipid is disclosed in JP2005-517739A.